Linkage studies in a series of early onset familial Alzheimer's disease families (EFAD) strongly suggested that the gene is located on chromosome 21 in the region 21q11.1-21q22.2. Two subsequent studies showed that the loci for EFAD and the amyloid (A4) protein were, in fact, 18 centimorgans apart. More recently, linkage studies on later onset families (greater than 60 years) excluded the area where the EFAD gene presumably is located. These results strongly suggest locus heterogeneity in familial Alzheimer's disease. Additional linkage studies are needed in order to: (1) verify the mapping of the EFAD gene to chromosome 21 and (2) to map the gene(s) for later onset FAD. This proposal plans to ascertain and make available the "raw material," i.e., cell lines from the most highly informative families in the United States, to researchers who are interested in mapping familial Alzheimer's disease. This proposal plans to ascertain familial cases of AD through the Alzheimer's Association, the ADRCs and the Consortium to Establish an Alzheimer's Disease Registry (CERAD) network. Family history questionnaires will help establish which families are potentially useful. After thorough investigation, those with the greatest potential will be chosen. At least one autopsy verified case will be ascertained and other at-risk family members will be examined. If the family meets the optimum criteria, blood will be obtained and lymphocytes transformed at Indiana and stored in two independent locations. Cell lines will be made available to qualified researchers. Linkage analysis will also be performed for researchers who are not conversant with this aspect of gene mapping.